Darbepoetin alfa: A new therapeutic agent for renal anemia

Darbepoetin alfa: A new therapeutic agent for renal anemia. Darbepoetin alfa is a super-sialylated analog of human erythropoietin that has a longer circulating half-life in vivo compared to both native and recombinant hormone. It has the same mechanism of action as erythropoietin, stimulating the same surface membrane receptor and triggering the same intracellular chain of events. An extra two N-linked carbohydrate chains, however, gives darbepoetin alfa greater metabolic stability in vivo, and its terminal half-life after intravenous administration is approximately three times longer than for intravenous erythropoietin. This in turn allows injections of the drug to be given less frequently, and studies have shown that once-weekly and once-every-other-week dosing can maintain the hemoglobin concentration in patients with renal anemia. The recommended starting dose for darbepoetin alfa is 0.45 μg/kg once weekly for both IV and SC administration, with subsequent titration based on the hemoglobin concentration. The adverse event profile is very similar to that seen with rHuEPO, and no antibodies have been detected in several thousand patients exposed to the drug, some of whom have been treated for up to five years now. Following a clinical research program that began in November 1996, darbepoetin alfa was finally approved by the European Commission in June 201, and by the FDA in September 201

Recombinant Human Erythropoietin in the Treatment of Renal Anaemia

This thesis is concerned with a study of the clinical and biological effects of recombinant human erythropoietin (EPO) which recently became available as a novel treatment for the anaemia of end-stage renal disease. The dissertation begins with an introductory chapter which contains a historical note and survey of the relevant published literature. In this section is included a review of the pathogenesis of renal anaemia, the traditional treatment options for this condition, the development of recombinant human EPO, the biochemistry and physiology of erythropoietin, the metabolic fate of EPO, and the early clinical trials with EPO. This is followed by seven chapters of original work undertaken in Cardiff between April 1988 and July 1990

Nutrition, anaemia and erythropoietin therapy

This article has no abstract

Intravenous Iron and Maintenance Hemodialysis

No abstract available

Measurement of hepcidin isoforms in human serum by liquid chromatography with high resolution mass spectrometry

Aim: Hepcidin-25 is the master regulator of iron homeostasis. N-truncated isoforms of hepcidin-25 have been identified (hepcidin-20, -22, -24), although data on the concentrations of these isoforms are sparse. Materials &amp; methods: Serum was mixed with aqueous formic acid, and the supernatant loaded onto a 96-well-SPE-plate. Eluted analytes were analyzed using LC–HR-MS. Forty-seven paired dipotassium-EDTA human plasma and serum samples were analyzed. Results: The LLOQ was 1 μg/l (all analytes). Accuracy and precision were acceptable. There was a good correlation (R2 &gt;0.90, all analytes) between matrices. The median (range) serum hepcidin-20, -22, -24 and -25 concentrations measured were 4 (1–40), 8 (2–20), 8 (1–50) and 39 (1–334) μg/l, respectively. Conclusion: LC–HR-MS is widely applicable to the measurement of hepcidin-25, and truncated isoforms. </jats:p

Authors' reply

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Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness

PRE‐dialysis survey on anaemia management

Background. The PRE‐dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre‐dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. Methods. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. Results. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration ≤11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r=0.43, P<0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration ≤11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. Conclusions. Few pre‐dialysis patients met the EBPG target for Hb concentration, despite regular nephrology car

Colorectal stents: Do we have enough evidence?

AbstractBackgroundThe use of colonic stents has significantly evolved over the last few years. Emergency surgery for colonic obstructions is usually associated with significant mortality, morbidity and often stoma formation. Colonic stents provide an alternative way to relieve colonic obstruction, and hence avoiding the risks associated with emergency surgery. This literature review aims to summarize the important current evidence regarding colorectal stenting and show whether further evaluation of the procedure is required.ResultsThe available large number of non-randomized studies suggests that Self-Expandable-Metal-Stents (SEMS) placement for acute colonic obstruction could be considered as safe and effective alternative to surgery in experienced hands either as a bridge to surgery or as a palliative measure. This evidence has led to SEMS being widely adopted. However, randomized evidence has begun to show the defects that are inherent in the low level evidence that has so far supported SEMS use and it may be that reports of randomized controlled trials may clarify the patient population where SEMS placement is appropriate.ConclusionWhile we are still waiting for the outcome of the multicentre randomized controlled trials in the UK and Europe, clinicians must be aware of the current evidence limitations and apply SEMS use pragmatically